Institute of Fundamental Technological Research
Polish Academy of Sciences

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Chengzhe Tian

University of Copenhagen (DK)


Recent publications
1.  Kellogg R.A., Tian C., Lipniacki T., Quake S.R., Tay S., Digital signaling decouples activation probability and population heterogeneity, eLife, ISSN: 2050-084X, DOI: 10.7554/eLife.08931, Vol.4, pp.e08931-1-26, 2015

Abstract:
Digital signaling enhances robustness of cellular decisions in noisy environments, but it is unclear how digital systems transmit temporal information about a stimulus. To understand how temporal input information is encoded and decoded by the NF-κB system, we studied transcription factor dynamics and gene regulation under dose- and duration-modulated inflammatory inputs. Mathematical modeling predicted and microfluidic single-cell experiments confirmed that integral of the stimulus (or area, concentration × duration) controls the fraction of cells that activate NF-κB in the population. However, stimulus temporal profile determined NF-κB dynamics, cell-to-cell variability, and gene expression phenotype. A sustained, weak stimulation lead to heterogeneous activation and delayed timing that is transmitted to gene expression. In contrast, a transient, strong stimulus with the same area caused rapid and uniform dynamics. These results show that digital NF-κB signaling enables multidimensional control of cellular phenotype via input profile, allowing parallel and independent control of single-cell activation probability and population heterogeneity.

Affiliations:
Kellogg R.A. - Eidgenössische Technische Hochschule Zürich (CH)
Tian C. - University of Copenhagen (DK)
Lipniacki T. - IPPT PAN
Quake S.R. - Stanford University (US)
Tay S. - Eidgenössische Technische Hochschule Zürich (CH)

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